impact of planarity of unfused aromatic molecules on g ... · school of pharmaceutical sciences,...

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Electronic Supplementory Information

Impact of Planarity of Unfused Aromatic Molecules on G-Quadruplex Binding:

Learning from Isaindigotone Derivatives

Jin-Qiang Hou, Jia-Heng Tan, Xiao-Xiao Wang, Shuo-Bin Chen, Si-Yuan Huang, Jin-Wu Yan, Shu-

Han Chen, Tian-Miao Ou, Hai-Bin Luo, Ding Li, Lian-Quan Gu,* Zhi-Shu Huang*

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People’s Republic of

China

*To whom correspondence should be addressed. Email [email protected] (L.-Q. Gu);

[email protected] (Z.-S. Huang), Tel 8620-39943056, Fax 8620-39943056.

Table of Contents

FRET-melting Results ........................................................................................................................................... S2

SPR Results ........................................................................................................................................................... S3 1H NMR Results .................................................................................................................................................... S4

Molecular Modeling Studies of the Interactions between Ligand and G-quadruplex ........................................... S5

NMR spectra of compounds 7a-7x ........................................................................................................................ S6

NOE Analysis of 4b, 4c, 4e, 6a, 6b, 6c and 6d ................................................................................................... S30

HPLC Purity Analysis of Compounds 7a-7x Using Two Different Systems ...................................................... S34

Electronic Supplementary Material (ESI) for Organic and Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2011

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FRET-melting Results

Fig S1. Representative FRET melting profiles of 0.2 μM F21T with 1μM isaindigotone derivatives

Fig S2. Representative FRET melting profiles of 0.2 μM F10T with 1μM isaindigotone derivatives


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SPR Results

Fig S3. SPR sensorgram overlay for binding of SYUID-5a (A), 7e (B) and 7h (C) to HTG21. The ligand concentrations in the flow solution are given in the figure.


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1H NMR Results

Fig S4. Titration of [d(TTAGGG)]4 with SYUID-5a, 7e and 7h. The 1H NMR spectra of the 600 MHz NMR is shown with increasing amounts of ligand added at 25 °C. Most DNA signals exhibited upfield shifts and were line-broadened with an increase in the ligand concentration. The assignments of some

signals are given in the spectra.


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Molecular Modeling Studies of the Interactions between Ligand and G-quadruplex

Fig S5. One hundred docking conformers of ligand-quadruplex complexes. A: 7e-quadruplex complex. B: 7h-quadruplex complex.

Fig S6. Time dependence of the RMSD of G-quartet heavy atoms (black) and ligand all atoms (red). A: 7e-quadruplex complex. B: 7h-quadruplex complex


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NMR spectra of compounds 7a-7x

1H NMR spectrum of 7a

13C NMR spectrum of 7a


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1H NMR spectrum of 7b

13C NMR spectrum of 7b


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1H NMR spectrum of 7c

13C NMR spectrum of 7c


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1H NMR spectrum of 7d

13C NMR spectrum of 7d


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1H NMR spectrum of 7e

13C NMR spectrum of 7e


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1H NMR spectrum of 7f

13C NMR spectrum of 7f


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1H NMR spectrum of 7g

1H NMR spectrum of 7g


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1H NMR spectrum of 7h

13C NMR spectrum of 7h


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1H NMR spectrum of 7i

13C NMR spectrum of 7i


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1H NMR spectrum of 7j

13C NMR spectrum of 7j


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1H NMR spectrum of 7k

13C NMR spectrum of 7k


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1H NMR spectrum of 7l

13C NMR spectrum of 7l


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1H NMR spectrum of 7m

13C NMR spectrum of 7m


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1H NMR spectrum of 7n

13C NMR spectrum of 7n


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1H NMR spectrum of 7o

13C NMR spectrum of 7o


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1H NMR spectrum of 7p

13C NMR spectrum of 7p


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1H NMR spectrum of 7q

13C NMR spectrum of 7q


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1H NMR spectrum of 7r

13C NMR spectrum of 7r


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1H NMR spectrum of 7s

13C NMR spectrum of 7s


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1H NMR spectrum of 7t

13C NMR spectrum of 7t


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1H NMR spectrum of 7u

13C NMR spectrum of 7u


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1H NMR spectrum of 7v

13C NMR spectrum of 7v


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1H NMR spectrum of 7w

13C NMR spectrum of 7w


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1H NMR spectrum of 7x

13C NMR spectrum of 7x


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NOE Analysis of 4b, 4c, 4e, 6a, 6b, 6c and 6d

NOE spectrum of 4b

NOE spectrum of 4c


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NOE spectrum of 4e

NOE spectrum of 6a


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NOE spectrum of 6b

NOE spectrum of 6c


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NOE spectrum of 6d


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HPLC Purity Analysis of Compounds 7a-7x Using Two Different Systems

Table1. HPLC Purity Analysis of Compounds 7a-7x a

Compound Purity(%) Methanol/Water Retention time (min) 7b 94 40/60 8.87 7c 100 40/60 15.31 7d 99 40/60 11.06 7e 94 40/60 9.20 7f 98 40/60 14.76 7g 98 40/60 11.66 7s 96 40/60 21.19 7t 99 45/55 13.88 7a 100 40/60 11.87 7q 99 40/60 20.71 7r 97 45/55 14.50 7h 91 40/60 10.96 7i 88 40/60 17.52 7j 100 40/60 13.99 7u 94 40/60 19.10 7v 96 45/55 14.50 7k 97 40/60 8.04 7l 100 40/60 15.44

7m 99 40/60 10.65 7n 99 40/60 8.49 7o 99 40/60 13.98 7p 100 40/60 10.98 7w 99 40/60 17.78 7x 98 45/55 12.57

a 0.1% TFA in MeOH and 0.1% aqueous TFA over 30 min (1 ml/min); Purity at 254nm.


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7a 7b

7c 7d

7e 7f

7g 7h

7i 7j

7k 7l


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7m 7n

7o 7p

7q 7r

7s 7t

7u 7v

7w 7x


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Table2. HPLC Purity Analysis of Compounds 7a-7x a

Compound Purity(%) Acetonitrile/Water Retention time (min) 7b 93 20/80 11.10 7c 99 20/80 18.62 7d 98 20/80 13.74 7e 92 20/80 12.86 7f 97 22/78 12.91 7g 97 20/80 17.23 7s 96 20/80 28.11 7t 99 20/80 37.63 7a 100 20/80 15.86 7q 99 20/80 20.95 7r 97 20/80 28.73 7h 99 20/80 14.67 7i 99 20/80 26.67 7j 99 20/80 17.07 7u 88 20/80 19.19 7v 85 20/80 26.26 7k 98 20/80 9.86 7l 100 20/80 19.01

7m 99 20/80 13.42 7n 97 20/80 11.98 7o 99 20/80 16.32 7p 99 20/80 17.30 7w 99 20/80 22.72 7x 99 20/80 29.78

a 0.1% TFA in acetonitrile and 0.1% aqueous TFA over 60 min (1 ml/min); Purity at 254nm.


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7a 7b

7c 7d

7e 7f

7g 7h

7i 7j

7k 7l


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7m 7n

7o 7p

7q 7r

7s 7t

7u 7v

7w 7x


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impact of planarity of unfused aromatic molecules on g ... · school of pharmaceutical sciences,...

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